AI Article Synopsis
- The study identifies a lack of sensitive diagnostic biomarkers for osteoporosis, highlighting the need for new biomarker discovery to improve early diagnosis and treatment.
- Researchers used GEO2R to screen and validate differentially expressed genes (DEGs) in blood samples from osteoporosis patients across two datasets, and utilized various databases to explore gene functions and drug interactions.
- The analysis prioritized six key DEGs (EGFR, HMOX1, PGR, CXCL10, CCL5, IL12B) that were significantly upregulated in osteoporosis patients, demonstrating strong potential for use as diagnostic markers.
Article Abstract
Background: Due to the lack of sensitive diagnostic biomarkers for osteoporosis (OP), there is an urgent need to identify and uncover biomarkers associated with the disease in order to facilitate early clinical diagnosis and effective intervention strategies.
Methods: GEO2R was employed to conduct a screening of differentially expressed genes (DEGs) within the transcriptome sequencing data obtained from blood samples of OP patients within the GSE163849 dataset. Subsequently, we conducted expression confirmation of the identified DEGs using an additional dataset, GSE35959. To further explore Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, MicroRNA (miRNA) interactions, and drug predictions, we employed the DAVID, miRTarBase, and DrugBank databases. For validation purposes, clinical OP samples paired with normal controls were collected from the Pakistani population. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression levels of DEGs and miRNA, while targeted bisulfite sequencing (bisulfite-seq) analysis was used to investigate methylation patterns. DNA and RNA from clinical OP and normal control samples were extracted using appropriate methods.
Results: Out of total identified 269 DEGs, EGFR (epidermal growth factor receptor), HMOX1 (heme oxygenase-1), PGR (progesterone receptor), CXCL10 (C-X-C motif chemokine ligand 10), CCL5 (C-C motif chemokine ligand 5), and IL12B (interleukin 12B) were prioritized as top DEGs in OP patients. Expression validation of these genes on additional Gene Expression Omnibus (GEO) dataset and Pakistani OP patients revealed consistent significant up-regulation of these genes in OP patients. Receiver operating characteristic (ROC) analysis demonstrated that these DEGs displayed considerable diagnostic accuracy for detecting OP. Targeted bisulfite-seq analysis further revealed that EGFR, HMOX1, PGR, CXCL10, CCL5, and IL12B were hypomethylated in OP patients. Moreover, has-miR-27a-5p, a common expression regulator of the EGFR, HMOX1, PGR, CXCL10, CCL5, and IL12B was also significantly down-regulated in OP patients.
Conclusion: The DEGs that have been identified hold significant potential for the future development of diagnostic and treatment approaches for OP in preclinical and clinical applications.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10641362 | PMC |
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